Back to Search
Start Over
Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice
- Source :
- Nature medicine
- Publication Year :
- 2016
-
Abstract
- The increasing global prevalence of obesity and its associated disorders points to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules that have mRNA expression profiles similar to that of celastrol, a naturally occurring compound that we previously identified as a leptin sensitizer. Through this process, we identified another naturally occurring compound, withaferin A, that also acts as a leptin sensitizer. We found that withaferin-A treatment of mice with diet-induced obesity (DIO) resulted in a 20-25% reduction of body weight, while also decreasing obesity-associated abnormalities, including hepatic steatosis. Withaferin-A treatment marginally affected the body weight of ob/ob and db/db mice, both of which are deficient in leptin signaling. In addition, withaferin A, unlike celastrol, has beneficial effects on glucose metabolism that occur independently of its leptin-sensitizing effect. Our results show that the metabolic abnormalities of DIO can be mitigated by sensitizing animals to endogenous leptin, and they indicate that withaferin A is a potential leptin sensitizer with additional antidiabetic actions.
- Subjects :
- 0301 basic medicine
Blood Glucose
Leptin
Fluorescent Antibody Technique
Mice, Obese
Pharmacology
chemistry.chemical_compound
Mice
Weight loss
2. Zero hunger
Glucose tolerance test
medicine.diagnostic_test
digestive, oral, and skin physiology
Fatty liver
General Medicine
Immunohistochemistry
3. Good health
Liver
Celastrol
medicine.symptom
Pentacyclic Triterpenes
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
STAT3 Transcription Factor
medicine.medical_specialty
Blotting, Western
Hypothalamus
Carbohydrate metabolism
Diet, High-Fat
Real-Time Polymerase Chain Reaction
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
medicine
Humans
Animals
Obesity
Withanolides
Body Weight
Glucose Tolerance Test
medicine.disease
Triterpenes
Fatty Liver
030104 developmental biology
Endocrinology
chemistry
Diabetes Mellitus, Type 2
Withaferin A
Steatosis
Subjects
Details
- ISSN :
- 1546170X
- Volume :
- 22
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....aed3a81a624386981b40a9b17f319a8b